Integrin‐dependent modulation of macrophage K+ channels and its impact on macrophage function has only recently been studied (Colden‐Stanfield, 2008). Parallel patch‐clamp and oxidative burst experiments were performed in murine bone marrow‐derived macrophages (BMDMs) with or without clustered very late antigen‐4 (VLA‐4) integrins. BMDMs cultured in suspension that were further incubated on uncoated polystyrene (POLY) for 5 h only possessed inwardly rectifying potassium (Kir) currents with a resting membrane potential of ‐57 mV. Ninety percent of BMDMs with clustered VLA‐4 integrins possessed both Kir and delayed rectifier potassium (Kdr) currents with a more depolarized resting membrane potential (‐47mV). Under identical experimental conditions basal and stimulated intracellular hydrogen peroxide production was measured. Basal and PMA‐stimulated oxidative burst activity was enhanced 5‐and 14‐fold in BMDMs with clustered VLA‐4 integrins, respectively. Although specific blockade of Kdr currents with margatoxin did not alter the VLA‐4‐augmented oxidative burst activity, exposure to the Kir blocker, CsCl, significantly reduced the enhanced response. These data suggest that VLA‐4 integrins modulate K+ currents to possibly enhance the ability of macrophages to mount a respiratory burst in an immune response. This research was supported by NHLBI K01 HL076628.